Histo: Renal Disease Pt.2 Flashcards
How does acute tubular injury lead to reduced GFR?
- Blockage of tubules by casts
- Leakage from tubules into interstitial space
- Secondary haemodynamic changes
Describe the histological appearance of ATN
Necrosis of short segments of tubules
What is acute tubulo-interstitial nephritis?
Inflammation of the renal interstitium, typically due to immune-mediated hypersensitivity reaction
Can be caused by infection and drugs (NSAIDs, antibiotics, diuretics, allopurinol, PPIs)
Describe the histological appearance of acute tubulo-interstital nephritis.
Heavy interstitial infiltration with eosinophil and granulomas
What are some key signs of acute glomerulonephritis?
- Oligo/anuria
- Haematuria
- Erythrocyte and leukocyte casts on MCS
What is rapidly progressive (crescentic) GN?
Most aggressive form of GN – can cause ESRF within weeks.
Presents as a nephritic syndrome, but oliguria and renal failure are more pronounced
What causes crescents to appear in acute glomerulonephritis?
Occurs in severe glomerulonephritis due to proliferation of macrophages & parietal cells in Bowman’s space which pushes glomerulus to one side
Describe the classification of acute crescentic glomerulonephritis.
Classification based on immunological findings:
- Type 1. Anti-GBM antibody (Goodpasture’s)
- Type 2. Immune complex mediated (SLE)
- Type 3. Pauci-immune (ANCA-associated - GPA)
NOTE: these can rapidly lead to irreversible renal failure
List some causes of immune complex-associated (type 2) crescentic glomerulonephritis.
- SLE
- IgA nephropathy
- Post-infectious glomerulonephritis
- HSP
What techniques can be used to visualise immune complexes in these diseases?
- Immunohistochemistry (fluorescence microscopy)
- Electron (light) microscopy
How does immune complex-associated crescentic GN appear on fluorescence microscopy?
Granular (lumpy bumpy) IgG immune complex deposition on GBM/mesangium
What are the antibodies directed against in anti-GBM disease?
How can these antibodies be detected?
- Against the C-terminal domain of type IV collagen (COL4-A3)
- Detected by serology
NOTE: these antibodies can cross-react with the alveolar basement membrane leading to pulmonary haemorrhage and haemoptysis
Describe the immunohistochemistry picture produced in anti-GBM disease
Linear deposition of IgG on the glomerular basement membrane
What are the main features of pauci-immune crescentic glomerulonephritis?
- Lack of / scanty glomerular immunoglobulin depositis
- Usually associated with ANCA
- Triggers neutrophil activation and glomerular necrosis
- Vasculitis (elsewhere) – particularly presenting as skin rashes or pulmonary haemorrhage
What is thrombotic microangiopathy?
- Damage to the endothelium in glomeruli, arteriols and arteries resulting in thrombosis
- Red cells can be damaged by fibrin causing MAHA or HUS
List some types of thrombotic microangiopathy.
HUS: Thrombi confined to kidneys
- Typical HUS - usually associated with diarrhoea caused by E.coli O157:H7 (outbreaks caused by children visiting petting zoos/eating undercooked meat)
- Atypical HUS (non-diarrhoea associated) - due to abnormal proteins in complement pathway/endothelium (can be familial)
- Triad - thrombocytopaenia, MAHA, renal damage
TTP: Thrombi occur throughout circulation, esp. in CNS
- A genetic / acquired deficiency of ADAMTS13
- Pentad - thrombocytopaenia, MAHA, renal damage, CNS abnormalities, fever
Also:
- Drugs, radiation, hypertension, scleroderma, antiphospholipid syndrome
What are the characteristic features of nephrotic syndrome?
- Proteinuria (>3.5 g/day or >300mg/mmol PCR)
- Hypoalbuminaemia
- Oedema
- Hyperlipidaemia
List some causes of nephrotic syndrome.
-
Primary glomerular disease (non-immune complex mediated)
- Minimal change disease
- Focal segmental glomerulosclerosis
-
Primary renal disease (immune complex mediated)
- Membranous glomerulonephritis
-
Systemic disease
- SLE
- Amyloidosis
- Diabetes mellitus
What is minimal change disease?
- Most common cause of nephrotic syndrome in children
- Glomeruli look normal on light microscopy, but electron microscopy shows loss of foot processes
- Generally responds well to steroids and immunosuppression
Describe the histological appearance of focal segmental glomerulosclerosis.
Focal and segmental glomerular consolidation and scarring
Hyalinosis
NOTE: this responds less well to immunosuppression
